Perioperative neurocognitive and functional neuroimaging trajectories in older APOE4 carriers compared with non-carriers: secondary analysis of a prospective cohort study

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Abstract

Background: Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. Methods: We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. Results: There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels. Conclusions: Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

Original languageEnglish
Pages (from-to)917-928
Number of pages12
JournalBritish Journal of Anaesthesia
Volume127
Issue number6
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
MB has received material support (i.e. EEG monitors) for a postoperative recovery study in older adults from Masimo, unrelated to this manuscript. MB has also received legal consulting fees related to postoperative cognition in older adults. JB acknowledges funding from Claret Medical , Inc. The other authors have no relevant conflicts to disclose.

Funding Information:
MB has received material support (i.e. EEG monitors) for a postoperative recovery study in older adults from Masimo, unrelated to this manuscript. MB has also received legal consulting fees related to postoperative cognition in older adults. JB acknowledges funding from Claret Medical, Inc. The other authors have no relevant conflicts to disclose.US National Institutes of Health (R01-HL130443 to JM and JB; U01-HL088942 to JM and JB; U01-AG050618 to JB), Duke Anaesthesiology departmental funds, and a mentored research grant from the International Anesthesia Research Society. MB acknowledges additional support from the Alzheimer's Drug Discovery Foundation (NIH grants T32 GM08600, R03AG050918, 1K76AG057022 to MB), Duke Claude D. Pepper Older American Independence Centre (P30AG028716), and William L. Young neuroscience research award from the Society for Neuroscience in Anaesthesiology and Critical Care (SNACC).

Funding Information:
US National Institutes of Health ( R01-HL130443 to JM and JB; U01-HL088942 to JM and JB; U01-AG050618 to JB), Duke Anaesthesiology departmental funds, and a mentored research grant from the International Anesthesia Research Society . MB acknowledges additional support from the Alzheimer’s Drug Discovery Foundation (NIH grants T32 GM08600 , R03AG050918 , 1K76AG057022 to MB), Duke Claude D. Pepper Older American Independence Centre ( P30AG028716 ), and William L. Young neuroscience research award from the Society for Neuroscience in Anaesthesiology and Critical Care (SNACC).

Publisher Copyright:
© 2021 British Journal of Anaesthesia

Keywords

  • APOE4
  • Alzheimer's disease
  • cerebrospinal fluid
  • functional MRI
  • intrinsic functional connectivity
  • neuroimaging
  • perioperative neurocognitive disorders
  • surgery

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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